Clinical outcomes in adults with aortic valve stenosis (AS) are predicted by symptom status, valve anatomy, hemodynamics and left ventricular (LV) systolic function. There is strong evidence that aortic valve replacement (AVR) increases survival and relieves symptoms in adults with symptoms due to severe valve obstruction.¹ However, the possible benefit of AVR in asymptomatic patients is less clear.

The 2014 AHA/ACC Valve Guidelines introduced a new classification of AS with four stages, defined by symptoms, leaflet anatomy, valve hemodynamics, and LV ejection fraction. Asymptomatic patients are classified as Stage A disease if they are at risk of developing AS but currently have normal leaflet opening without valve obstruction, for example, a young patient with a normally functioning bicuspid valve or an older adult with aortic valve sclerosis. Patients are considered to have Stage B disease if there is evidence of progressive leaflet calcification and thickening with reduced leaflet motion resulting mild to moderate valve obstruction. Stage A and Stage B AS do not benefit from AVR, although standard cardiac risk factor reduction, including treatment of hypertension, is important in these patient groups.²

Severe AS is defined by current guidelines as calcified or thickened valve leaflets with reduced systolic opening and an antegrade velocity across the valve of 4.0 m/s or higher, equivalent to a mean systolic transaortic pressure gradient of 40 mm Hg or higher. Typically, aortic valve area is 1.0 cm² or less although this is not required to meet the criteria of severe AS. Patients with asymptomatic severe AS and an LV ejection fraction of 50% or higher are recognized as Stage C1 AS and those with LV systolic dysfunction are recognized as Stage C2 AS.

Figure 1 Figure 2

Management of asymptomatic patients with severe AS is particularly challenging. Many patients remain asymptomatic for years despite a significantly high velocity through the valve. In addition, patients who are truly asymptomatic will not have improvement in symptoms after AVR.³ Further, survival during the asymptomatic phase is similar to age-matched controls with a low risk of sudden death (<1% per year), if frequent monitoring is pursued. Thus, it is difficult to justify the risk of surgical (SAVR) or transcatheter (TAVR) AVR and the long-term risk of a prosthetic valve for most patients with asymptomatic severe AS.

Thus, the first step in management of the patient with severe AS is to ensure the patient actually is asymptomatic based on a detailed discussion including any changes in levels of physical activity and directed questions about exertional dyspnea, dizziness or chest discomfort. In those with equivocal symptoms or the inability to fully assess symptoms due to lifestyle limitations, an exercise stress test may be helpful. If symptoms are provoked by exercise testing, the patient has severe symptomatic (Stage D) AS and AVR should be considered. An exercise capacity lower than expected for age and sex or a blunted rise in blood pressure with exercise raises concern that the stenotic valve is limiting the augmentation in cardiac output needed to meet increased metabolic demands. Measurement of beta-type natriuretic peptide (BNP) levels also may be useful in further risk stratification of those with asymptomatic severe AS.⁴

In initially asymptomatic adults with severe AS, symptoms often develop insidiously and may not be recognized by the patient until late in the disease course. Thus, the second step in patient management is periodic monitoring of symptom status, valve hemodynamics and LV systolic function. In asymptomatic adults with severe AS, the rate of progression to symptoms is high, with an event-free survival of only 30% to 50% at 2 years.⁵ Echocardiography is recommended for reevaluation of asymptomatic patients who have no change in symptoms at intervals of 6 to 12 months with more frequent monitoring for any change in symptoms or physical examination findings.

However, there is evidence to support a recommendation of AVR for some subgroups of asymptomatic patients with severe AS:

• Class I: AVR is recommended for Stage C2 AS (Asymptomatic severe AS with an LV ejection fraction < 50%). In asymptomatic patients with severe AS and an LV ejection fraction < 50% AVR improves survival as compared to those who are medically treated.⁶ In some cases, the low LV ejection fraction is due to excessive afterload caused by the valve, which will improve significantly after AVR. However, even when LV dysfunction is secondary to other causes, survival is still improved after AVR.
  
  
• Class I: AVR is recommended in adults with asymptomatic severe AS who are undergoing other cardiac surgery. Studies have shown that disease progression occurs in nearly all those with asymptomatic severe AS disease. Symptom onset usually occurs within two to five years when the aortic velocity is >4 m/s, therefore the additive benefit of AVR at the time of other cardiac surgery outweighs the risk of reoperation within 5 years.⁷
  
  
• Class IIa: AVR is reasonable for asymptomatic patients with very severe AS (stage C1 aortic velocity >5m/s) and low surgical risk. In this group of patients, the risk of symptom onset is approximately 50% at two years. The rate of symptoms onset and adverse cardiac events with very severe AS is even higher than those with severe AS.⁸ Therefore, elective AVR should be considered if the surgical risk is low rather than waiting until symptom development.
  
  
• Class IIa: AVR is reasonable in asymptomatic patients (stage C1) with severe AS and decreased exercise tolerance or an exercise fall in BP. Exercise testing may be helpful in clarifying symptom status in patients with severe AS.⁹ If symptoms are provoked by exercise testing, the patient has severe symptomatic (Stage D) AS and AVR is recommended. In addition, AVR should be considered if there is a drop in systolic blood pressure below baseline, a failure of blood pressure to increase by 20 mmHg or more, or if there is a significant reduction in exercise tolerance.
  
  
• Class IIb: AVR may be considered for asymptomatic patients with severe AS (stage C1) and rapid disease progression if surgical risk is low. Rapid progression is defined as an increase in aortic velocity of 0.3 m per second per year or greater. Predictors of rapid progression include older age, more severe valve calcification and a faster rate of progression. In this group of patients, AVR may be considered based on surgical risk and patient preference.¹⁰

Overall, the timing of intervention is aligned closely with the new definitions of valve disease stages. There continues to be significant emphasis on the presence of symptoms to decide on the timing of intervention with a few exceptions, as outlined above, where there is clear benefit in intervening sooner.

References

1. Otto CM, Prendergast B. "Aortic-valve stenosis - from patients at risk to severe valve obstruction." N Engl J Med 371 (2014): 744-56.
2. Nishimura RA, Otto CM, Bonow RO, et al. "2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines." J Am Coll Cardiol 63 (2014): 2438-88.
3. Otto CM, Nishimura RA. "New ACC/AHA valve guidelines: aligning definitions of aortic stenosis severity with treatment recommendations." Heart 100 (2014): 902-4.
4. Capoulade R, Magne J, et al. "Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with severe asymptomatic aortic stenosis." Heart 100 (2014): 1606-12.
5. Stewart RA, Kerr AJ, Whalley GA, Legget ME, Zeng I, Williams MJ, Lainchbury J, Hamer A, Doughty R, Richards MA, White HD; New Zealand Heart Valve Study Investigators. Left ventricular systolic and diastolic function assessed by tissue Doppler imaging and outcome in asymptomatic aortic stenosis. Eur Heart J. 2010 Sep;31(18):2216-22.
6. Connolly HM, Oh JK, et al. "Aortic valve replacement for aortic stenosis with severe left ventricular dysfunction. Prognostic indicators." Circulation 95 (1997): 2395-400.
7. Smith WT, Ferguson TG Jr, et al. "Should coronary artery bypass graft surgery patients with mild or moderate aortic stenosis undergo concomitant aortic valve replacement? A decision analysis approach to the surgical dilemma." J Am Coll Cardiol 44 (2004): 1241-7.
8. Rosenhek R, Zilberszac R, et al. "Natural history of very severe aortic stenosis." Circulation 121 (2010): 151-6.
9. Marechaux S, Hachicha Z, et al. "Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis." Eur Heart J 31 (2010): 1390-7.
10. Pilgrim T, Englberger L, Rothenbühler M, Stortecky S, Ceylan O, O'Sullivan CJ, Huber C, Praz F, Buellesfeld L, Langhammer B, Meier B, Jüni P, Carrel T, Windecker S, Wenaweser P. Long-term outcome of elderly patients with severe aortic stenosis as a function of treatment modality. Heart. 2015;101(1):30-6.

Keywords: Aortic Valve, Aortic Valve Stenosis, Blood Pressure, Calcinosis, Cardiac Output, Cardiac Surgical Procedures, Death, Sudden, Disease Progression, Dizziness, Dyspnea, Echocardiography, Exercise Test, Exercise Tolerance, Heart Defects, Congenital, Heart Valve Diseases, Hypertension, Life Style, Mitral Valve, Natriuretic Peptides, Risk Factors, Sclerosis, Systole, Ventricular Function, Left

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